Subcutaneous recombinant gamma interferon in cancer patients: toxicity, pharmacokinetics, and immunomodulatory effects.

摘要: Recombinant gamma interferon (rγ-IFN) was administered s. c. daily to 26 patients with advanced cancer. Patients were assigned one of six doses: 0.5, 1, 2, 4, 6, or 8 million units (MU)/m2 per d. The major toxicities an influenza-like syndrome and fever, seen in all patients. Dose limiting toxicity occurred 4 treated at MU/m2. One patient nodular poorly differentiated lymphocytic lymphoma had a mixed response, two renal cell cancer have stabilization disease for >10 >12 months. Pharmacokinetic analysis, by radioimmunoassay, revealed mean serum rγ-IFN concentrations up 17 ng/ml, maximal levels noted 6 13 h after injection. In vivo immunomodulation assessed natural killer (NK) cytotoxicity, monocyte activation as determined surface expression HLA-Dr, peripheral blood mononuclear phenotype analysis flow cytometry. T4/T8 ratio increased from 2.1 pretreatment 4.1 24 treatment, but returned baseline 7 28 days treatment. Augmentation NK function Monocyte HLA-Dr treatment the three lowest doses. conclusion, can be easily on outpatient basis minimal local skin toxicity, results prolonged levels, is associated immunological changes potential antitumor significance. Further study immunomodulatory effects induced indicated help define optimal regimen.